1. 1

2. 2 The authors declare no conflicts of interest No financial support was taken for this cross-sectional study

3. ASNR 2015 Annual Meeting Abstract No: EP-04 Submission Number: 1813 Hormone replacement therapy-related changes in the early postmenopausal period (critical window): an in vivo brain proton magnetic resonance spectroscopy study Kamran Mahmutyazıcıoglu 1, Fahri Halit Besir 2, Mustafa Bardakci 3, Hamit Alper Tanrıverdi 4, Handan Ankarali 5 1 Department of Radiology, Faculty of Medicine, Fatih University Sema Training Hospital, İstanbul, Turkey 2 Department of Radiology, Duzce University Faculty of Medicine, Duzce, Turkey 3 Department of Radiology, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey 4 Department of Obstetrics and Gynecology, Faculty of Medicine, Bülent Ecevit University,Zonguldak, Turkey 5 Department of Statistics, Duzce University Faculty of Medicine, Duzce, Turkey 3

4. Purpose Hormonal replacement therapy (HRT) is a medical treatment to relieve the symptoms of menopause in surgically or naturally postmenopausal women Magnetic resonance spectroscopy (MRS) is an in vivo method used to study brain metabolism; in particular, the changes that occur during aging and cognitive diseases have attracted interest.

5. Purpose However, brain MRS data on the effect of HRT in the postmenopausal period are lacking. We sought todetermine whether there are metabolic changes related with HRT usage in the brains of healthy postmenopausal women with no cognitive complaints who started HRT in the early postmenopausal period (critical window).

6. Materials and Methods The cross-sectional study was enrolling postmenopausal women. Healthy, literate postmenopausal women, between 45 and 65 years old, were included in the study. Postmenopausal women in the present study were assembled into 2 groups, as HRT users and non-HRT users. The 2 groups were matched for age, education, and postmenopausal period.

7. Materials and Methods

8. MR examinations were conducted with a 1.5 T scanner (Gyroscan Intera, Philips, Best, the Netherlands). A standard head coil was used for conventional MR imaging and MRS.

9. Sixty-eight postmenopausal women aged between 45 and 55 years old were included in the study. Of these, 21 subjects were excluded from the study due to anxiety disorder (2 subjects), depression (5 subjects), vertebrobasilar insufficiency (1 subject), and hypertension or heart failure (13 subjects). Of the 47 subjects included in the study, 21 (45%) used HRT and 26 (55%) did not. Results

10. The results of the comparison of HRT users and nonusers in terms of age and duration of menopause are given in Table. The differences between the 2 groups regarding age and duration of menopause were not statistically significant.

11. Descriptive statistics of NAA/Cr, Cho/Cr, and NAA/Cho ratios according to groups and brain regions are shown in Table. Results

12. The 4 brain regions did not differ significantly in terms of NAA/Cr ratio (P = 0.079) and this result was the same for both groups (P = 0.560). Results

13. Cho/Cr ratio of the HRT user group was significantly higher in all 4 regions when controlling for the differences between brain region and the group-by-region interaction (P = 0.05)

14. Results NAA/Cho ratios correlated negatively with duration of menopause when controlling for the effect of age (r=–0.350, p=0.05

15. Results NAA/Cho ratio of the HRT- user group was significantly lower in all 4 brain regions when controlling for the differences between brain region and the group-by region interaction (p=0.007)

16.  The critical period or window theory suggests a beneficial effect of estrogen therapy in the early postmenopausal stage. The present findings of decreased NAA/Cho and elevated Cho/Cr do not support this theory and argue against the neuroprotective effect of HRT in early postmenopausal women during the critical period. It is unclear whether our results were affected by the addition of progestin to estrogen. Because all hormone treated women in our study received tibolone, which has combined estrogenic and progestogenic properties, our study provides no evidence regarding the effect of unopposed estrogen therapy on neuronal integrity. Further comparative studies are necessary to resolve this issue. Conclusions

17.  The current data suggest, but do not prove, that postmenopausal HRT with tibolone, a synthetic steroid with estrogenic, progestogenic, and androgenic properties, do not have a protective effect on the neurochemical structure of the brain in selected regions. Since this study is of a cross- sectional design, further longitudinal studies are needed to validate this finding. Conclusions

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